PAC3421 Lecture Notes - Lecture 28: Inflammatory Bowel Disease, Immunosuppressive Drug, Bone Marrow Suppression
26 Jun 2018
School
Department
Course
Professor
Inflammatory Bowel Disease – Ulcerative Colitis + Crohn’s Disease
How do we treat IBD & why? - induce remission / maintain remission - prevention of disease complications eg.
pain, infections, fistulas, surgery – prevent nutritional deficiencies - optimisation of surgical outcomes
5-Aminosalicylates eg. mesalazine, balsalazide, olsalazine, sulfasalazine
- standard Tx for mild -> mod UC - less evidence in CD (OK in mild disease)
- sulfasalazine: AE include yellow-orange skin, tears, dark orange urine
- usually dose related!! check if renal impairment
- nausea, rash, headache, macrocytosis (enlargement of red blood cells)
- rarely haemolysis, pneumonitis, agranulocytosis (lowered white blood cell count)
- if there is an allergy to sulphonamides -> contraindicated
Corticosteroids eg. Oral prednisolone (some people may need IV)
- used to induce remission (UC + CD) NOT recommended for maintenance, effective and fast acting
oBudesonide: ↓ SE due to ↓ abs
Thiopurines eg. azathioprine, mercaptopurine
- mild to mod IBD, used as maintenance therapy w/ biologic therapy
- commenced in acute setting but 1-3 mons for full effect
- AE: nausea, malaise, flu-like symptoms, sun sensitivity, rash
more serious: pancreatitis, arthralgia (pain in a joint), myelosupression, hepatitis, infections
Methotrexate (for CD) -> induces remission, takes 6-8 weeks
- prevents relapse in Pts who can’t take azathioprine/mercaptopurine
- more effective when parenterally injected
- poor evidence for efficacy for UC, unacceptable SE
- SE: rash, nausea, diarrhoea, bone marrow suppression, infections, cirrhosis (monitor liver function)
- need folic acid!!
Cyclosporin (calcineurin inhibitor)
- calcineurin normally promotes cytokine up regulation -> stimulate B and T cell prolif + diff →
inflammation
- rescue therapy in acute severe colitis
- need to watch out for CYP interactions, renal dysfunction, neurotoxicity, ↓ Mg, HT, ↑ chol
Anti-TNFα Antibodies eg. infliximab (IV), adalimumab (SC) – both have similar effectiveness
- binds to Tumour Necrosis Factor alpha (TNFα) which normally regulates inflammation
- mod to severe UC/ CD
AE: infusion / injection site reactions, drug-induced lupus, infections eg. reactivation of tuberculosis,
worsening of congestive heart failure
Vedolizumab (monoclonal antibody)
- gut specific – binds to α4β7 integrin R, block it from interacting with MAdCAM-1 / mucosal addressin
cell adhesion molecule-1
IBD: test that can be performed to exclude infection? -> stool culture
Important to take history: - bowel symptoms – onset of symptoms + history of travel (could be traveller’s
diarrhoea instead of UC/ CD) – other med – family history (AI diseases) smoking – bowel cancer – previous ab
surgery – social history
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Inflammatory bowel disease ulcerative colitis + crohn"s disease. Induce remission / maintain remission - prevention of disease complications eg. pain, infections, fistulas, surgery prevent nutritional deficiencies - optimisation of surgical outcomes. 5-aminosalicylates eg. mesalazine, balsalazide, olsalazine, sulfasalazine standard tx for mild -> mod uc - less evidence in cd (ok in mild disease) Sulfasalazine: ae include yellow-orange skin, tears, dark orange urine. Usually dose related!! check if renal impairment. Nausea, rash, headache, macrocytosis (enlargement of red blood cells) Rarely haemolysis, pneumonitis, agranulocytosis (lowered white blood cell count) If there is an allergy to sulphonamides -> contraindicated. Corticosteroids eg. oral prednisolone (some people may need iv) used to induce remission (uc + cd) not recommended for maintenance, effective and fast acting: budesonide: se due to abs. Mild to mod ibd, used as maintenance therapy w/ biologic therapy commenced in acute setting but 1-3 mons for full effect.
